Lysophospholipids affect fundamental cellular functions that include proliferation, differentiation, survival, migration, adhesion, invasion, and morphogensis. Abnormal functions influence many biological processes leading to disease that include, but are not limited to fibrotic disease, inflammation, cancer and peripheral nerve injury. Lysophosphatidic acid (LPA) is a lysophospholipid that has been shown to act through specific G protein-coupled receptors (GPCRs) in an autocrine and paracrine fashion. Antagonists of the LPA receptors find use in the treatment of diseases, disorders or conditions in which LPA plays a role.
Agents that interact with the lysophosphatidic acid receptors [LPARs] to reduce signal transduction through those receptors (i.e., by competitive or noncompetitive inhibition or acting as inverse agonists) reduce manifestations of the diseases described herein. Diseases and conditions whose etiology, progression or persistence is effected by in whole or in part by signaling through the lysophosphatidic acid receptor subtype 1 (LPA1R) are considered LPA-dependent. New agents having therapeutic utility for treating those LPA-dependent and other conditions and diseases described herein are needed.